This Mentored Patient-Oriented Research Career Development award (K23) application is a request for funding to support the training and research activities for Roberto S. Kalil, M.D. to become an independent investigator in cardiovascular disease related to kidney transplantation. Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Kidney allograft survival had improved dramatically in the last decade without a parallel improvement in patient survival. Following transplantation, patients continue to experiment an accelerated form of atherosclerosis. Premature death from atherosclerotic cardiovascular disease in patients with continuous allograft function is the leading cause of mortality, and one of the main causes of transplant failure, the so-called death with allograft function. This rate is 10-20 times higher than the observed in the general population. This application includes an integrated program of training and research that utilizes the resources of the General Clinical Research Center, the Human Cardiovascular Physiology Laboratory, the Radiology Department, and the Department of Biostatistics and Epidemiology at the College of Public Health. The role of endothelial dysfunction and coronary artery calcifications in cardiovascular mortality and events in recipients of a kidney transplants have not been studied. We propose to longitudinally study endothelial function and coronary artery calcification before the kidney transplant, and sequentially after the transplant procedure with a total of 7 years of follow up. The primary goal is to explain whether amelioration in endothelial function following a kidney transplant is a predictor of progression/regression of atherosclerosis measured by coronary artery calcification, and overall cardiovascular morbidity/mortality at 7 years. Sequential measurements of newer biomarkers of inflammation including asymmetric dimethylarginine (ADMA) and isoprostanes will be performed along with the proposed non-invasive tests as a possible mechanistic explanation for the observed results. Identification of new, non-invasive diagnostic tools, as well as blood tests that predict cardiovascular complications in the early period following a kidney transplant are critical to improve survival of recipients of kidney transplantation in the United States. [unreadable] [unreadable] [unreadable]